The first mitochondrial 5-methylcytosine map in a non-model teleost (Oreochromis niloticus) reveals extensive strand-specific and non-CpG methylation

Artem Nedoluzhko,Robin Mjelle,Maria Renström,Kaja H Skjærven,Francesc Piferrer,Jorge M.O Fernandes

doi:10.1016/j.ygeno.2021.07.007

Abstract

DNA methylation is one of the main epigenetic mechanisms that regulate gene expression in a manner that depends on the genomic context and varies considerably across taxa. This DNA modification was first found in nuclear genomes of eukaryote several decades ago and it has also been described in mitochondrial DNA. It has recently been shown that mitochondrial DNA is extensively methylated in mammals and other vertebrates. Our current knowledge of mitochondrial DNA methylation in fish is very limited, especially in non-model teleosts. In this study, using whole-genome bisulfite sequencing, we determined methylation patterns within non-CpG (CH) and CpG (CG) contexts in the mitochondrial genome of Nile tilapia, a non-model teleost of high economic importance. Our results demonstrate the presence of mitochondrial DNA methylation in this species predominantly within a non-CpG context, similarly to mammals. We found a strand-specific distribution of methylation, in which highly methylated cytosines were located on the minus strand. The D-loop region had the highest mean methylation level among all mitochondrial loci. Our data provide new insights into the potential role of epigenetic mechanisms in regulating metabolic flexibility of mitochondria in fish, with implications in various biological processes, such as growth and development.

Highlights

The mitochondrion is a cellular organelle that plays a central role in the regulation of respiration and metabolic processes [1], and contains its own genome, which is known as mitochondrial DNA or mitogenome
The total number of reads generated from five specimens ranged from 16,335,889 to 16,960,827 per whole-genome bisulfite sequencing (WGBS)-library (NCBI accession numbers are presented in Supplementary Table 2)
The low 5mC methylation level in mitogenomes could be related to its specific usage and because it is less prevalent than 6mA methylation in prokaryotic genomes [58,59]

Summary

Introduction

The mitochondrion is a cellular organelle that plays a central role in the regulation of respiration and metabolic processes [1], and contains its own genome, which is known as mitochondrial DNA (mtDNA) or mitogenome. Mitochondrial epigenetics takes its roots at the beginning of the 1970s [3] but the first studies could not find evidence of mtDNA methylation in humans and other vertebrates [4]. The mitochondrion plays an important role in regulating the energetic processes in liver as well as in the complex regulation of fish growth through the hepatosomatic axis [8]. Mecha nisms of mitogenome functionality (including mtDNA methylation) are still unexplored in teleosts, the most abundant group containing 96% of all fishes and accounting for half of all extant vertebrates [9]

Methods

Results

Conclusion